The role of glia in neuropathic pain

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K10987
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Osaka Medical College
• Principal Investigator: Minami Toshiaki 大阪医科大学, 医学部, 教授 (00257841)
• Co-Investigator(Kenkyū-buntansha): 藤原 淳 大阪医科大学, 医学部, 助教 (00773516) ; 森本 賢治 大阪医科大学, 医学部, 助教 (20388250) ; 上野 健史 大阪医科大学, 医学部, 助教 (70782283) ; 中尾 謙太 大阪医科大学, 医学部, 助教 (50815719)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: がん性疼痛 / 神経障害性疼痛 / 脊髄 / アクロメリン酸 / アストロサイト / ミクログリア

Outline of Final Research Achievements

Neuropathic pain, resulting from peripheral nerve injury, is characterized by spontaneous and long-lasting pain, hyperalgesia, and allodynia. Peripheral nerve injury triggers long-term plastic changes along sensory pathways. Synaptic plasticity is a key mechanism for neuropathic pain. Bone cancer pain control is difficult because it includes various characteristics of pain such as nociceptic and neuropathic pain.
We investigated the effect of MMP-9 on cancer pain in mouse bone metastasis model. The pain behavior was significantly alleviated by MMP-9 inhibitor. MMP-9 expression was significantly elevated in the bone tissue in the early-phase and in the ipsilateral spinal cord in the late-phase.
Stiripentol, an effective antiepileptic drug, was recently shown to act as an inhibitor of lactate dehydrogenase in astrocytes. We demonstrated that stiripentol was effective against neuropathic pain and suggested that the astrocyte-neuron lactate shuttle was involved in such pain.

Free Research Field

疼痛治療学

Academic Significance and Societal Importance of the Research Achievements

がん性疼痛は、侵害受容性疼痛、神経障害性疼痛が混在し難治性であり約20%は薬剤に抵抗を示す。世界保健機構（WHO）では「がん性疼痛は治療できる症状であり、治療すべき症状である」と提言している。神経障害性疼痛やがん性疼痛の病態解明を進めることにより、薬剤抵抗性疼痛の根治療法確立に向け大きく前進する。